A Randomized, Double Blind, Comparative Study of Dideoxycytidine (ddC) Alone or ddC/AZT Combination Versus Zidovudine (ZDV) Alone in Patients With HIV Infection Who Have Received Prior ZDV Therapy

October 26, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To evaluate the safety of zalcitabine (dideoxycytidine; ddC) alone and in combination with zidovudine (AZT) versus AZT alone when administered to asymptomatic patients with a CD4 count = or < 200 cells/mm3 and symptomatic patients with a CD4 count = or < 300 cells/mm3. To compare the effectiveness of ddC alone and in combination with AZT versus AZT alone.

ddC has been shown to demonstrate an antiviral effect. AZT has been shown to significantly decrease mortality and reduce the frequency of opportunistic infections in patients with AIDS or advanced ARC. After 1 year of AZT therapy, the effectiveness tends to diminish and patients progress with more opportunistic infections and higher mortality rates. Because of the demonstrated antiviral activity, absence of hematologic toxicity, and lack of cross tolerance in laboratory studies of ddC, a study to investigate the long-term effectiveness of ddC in patients with HIV infection who have received AZT therapy is warranted.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

ddC has been shown to demonstrate an antiviral effect. AZT has been shown to significantly decrease mortality and reduce the frequency of opportunistic infections in patients with AIDS or advanced ARC. After 1 year of AZT therapy, the effectiveness tends to diminish and patients progress with more opportunistic infections and higher mortality rates. Because of the demonstrated antiviral activity, absence of hematologic toxicity, and lack of cross tolerance in laboratory studies of ddC, a study to investigate the long-term effectiveness of ddC in patients with HIV infection who have received AZT therapy is warranted.

Patients are randomly assigned to 1 of 3 treatment groups. In study arm 1, patients receive AZT plus ddC placebo. In study arm 2, patients receive ddC plus AZT placebo capsules. In study arm 3, patients receive ddC plus AZT. Patients are seen every other week for first 8 weeks and monthly thereafter. Patients are stratified by HIV disease status, length of time receiving AZT, and systemic or local Pneumocystis carinii pneumonia (PCP) prophylaxis. Patients who reach a clinical AIDS-defining endpoint are offered open-label combination therapy.

Study Type

Interventional

Enrollment

750

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA CARE Center CRS
      • Los Angeles, California, United States, 90033
        • USC CRS
      • San Diego, California, United States, 92103
        • UCSD Maternal, Child, and Adolescent HIV CRS
      • San Diego, California, United States
        • Ucsd, Avrc Crs
      • San Francisco, California, United States
        • Ucsf Aids Crs
      • Torrance, California, United States, 90502
        • Harbor-UCLA Med. Ctr. CRS
    • Colorado
      • Aurora, Colorado, United States
        • University of Colorado Hospital CRS
    • Florida
      • Miami, Florida, United States, 33136
        • Univ. of Miami AIDS CRS
    • Illinois
      • Chicago, Illinois, United States
        • Northwestern University CRS
      • Chicago, Illinois, United States
        • Rush Univ. Med. Ctr. ACTG CRS
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
    • Louisiana
      • New Orleans, Louisiana, United States
        • Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
      • New Orleans, Louisiana, United States
        • Tulane Hemophilia Treatment Ctr.
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Adult AIDS CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • HMS - Children's Hosp. Boston, Div. of Infectious Diseases
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital ACTG CRS
      • Boston, Massachusetts, United States, 02118
        • Bmc Actg Crs
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med. Ctr., ACTG CRS
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - East Campus A0102 CRS
      • Boston, Massachusetts, United States
        • Brigham and Women's Hosp., Div. of Infectious Disease
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, ACTU
    • Missouri
      • Saint Louis, Missouri, United States
        • Washington U CRS
      • Saint Louis, Missouri, United States
        • St. Louis ConnectCare, Infectious Diseases Clinic
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • NJ Med. School CRS
    • New York
      • Buffalo, New York, United States, 14215
        • SUNY - Buffalo, Erie County Medical Ctr.
      • New York, New York, United States, 10021
        • Cornell University A2201
      • New York, New York, United States, 10016
        • NYU Med. Ctr., Dept. of Medicine
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Ctr.
      • New York, New York, United States
        • NY Univ. HIV/AIDS CRS
      • New York, New York, United States, 10029
        • Beth Israel Med. Ctr. (Mt. Sinai)
      • Rochester, New York, United States
        • Univ. of Rochester ACTG CRS
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Unc Aids Crs
      • Charlotte, North Carolina, United States
        • Carolinas HealthCare System, Carolinas Med. Ctr.
      • Durham, North Carolina, United States, 27710
        • Duke Univ. Med. Ctr. Adult CRS
      • Greensboro, North Carolina, United States
        • Regional Center for Infectious Disease, Wendover Medical Center CRS
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Univ. of Cincinnati CRS
      • Cleveland, Ohio, United States, 44106
        • Case CRS
      • Columbus, Ohio, United States, 43210
        • The Ohio State Univ. AIDS CRS
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Pitt CRS
    • Washington
      • Seattle, Washington, United States, 98122
        • University of Washington AIDS CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Required:

  • Zidovudine (AZT) = or > 300 mg/day for 6 weeks prior to study entry.

Allowed:

  • Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP), candidiasis, and herpes.
  • 21 day course of adjuvant systemic corticosteroids for moderate to severe PCP.
  • Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole, ketoconazole, acyclovir, ganciclovir, or medications for tuberculosis or Mycobacterium avium for patients who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes virus infections, cytomegalovirus infections, tuberculosis or Mycobacterium avium intracellulare.
  • 14 day course of metronidazole.
  • Erythropoietin and megace if clinically indicated.
  • Isoniazid if patient has no peripheral neuropathy at entry and is taking pyridoxine = or > 50 mg/day concomitantly.
  • Phenytoin if patient has < grade 2 peripheral neuropathy at entry and has been stable on phenytoin = or > 3 months.

Patients must have:

  • Ability and willingness to give informed consent.
  • Written informed consent from a parent or guardian if < 18 years old.
  • Been tolerating zidovudine (AZT) therapy.
  • Diagnosis of HIV infection.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Kaposi's sarcoma or other malignancy requiring therapy.
  • Active opportunistic infections.
  • Peripheral neuropathy as manifested by complaints of moderate pain, burning, numbness, or tingling in hands/arms or feet/legs; moderate sensory deficit in the upper or lower extremities; or motor weakness in the upper or lower extremities.

Concurrent Medication:

Excluded:

  • Other experimental medications.
  • Other anti-HIV drugs.
  • Biologic response modifiers.
  • Cytotoxic chemotherapy.
  • Drugs that could cause peripheral neuropathy including phenytoin not specifically allowed, hydralazine, nitrofurantoin, vincristine, cisplatinum, dapsone, disulfiram, and diethyldithiocarbamate.

Concurrent Treatment:

Excluded:

  • Radiation therapy.

Patients with the following are excluded:

  • Active opportunistic infection. Must have ended acute therapy at least 14 days prior to study entry.
  • Peripheral neuropathy = or > grade 2.
  • History of intolerance to 500 to 600 mg/day of zidovudine (AZT) as manifested by the same recurrent grade 3 toxicity requiring dose interruptions and dose reductions to < 500 mg/day or any prior grade 4 toxicity.
  • Prior development of peripheral neuropathy on ddI = or > grade 2.

Prior Medication:

Excluded:

  • Dideoxycytidine (ddC).

Required:

  • Zidovudine (AZT) for total of at least 24 weeks; and included within that time period, AZT = or > 300 mg/day for 6 weeks prior to the study entry.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Hoffmann-La Roche
Glaxo Wellcome

Investigators

  • Study Chair: A Collier

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

May 1, 1993

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 2, 2021

Last Update Submitted That Met QC Criteria

October 26, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 155
  • 11130 (DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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